{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:27:42Z","timestamp":1787059662889,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":737,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Group 3 innate lymphocytes (ILC3s) rapidly respond to invading pathogens or inflammatory signals, which requires shifting cellular metabolic demands. Metabolic adaptations regulating ILC3 function are not completely understood. Polyamines are polycationic metabolites that have diverse roles in cellular functions and in immunity regulate immune cell biology, including Th17 cells. Whether polyamines play a role in ILC3 activation is unknown. In this article, we report that the polyamine synthesis pathway is important for ILC3 activation. IL-23\u2013activated mouse ILC3s upregulate ornithine decarboxylase, the enzyme catalyzing the rate-limiting step of the conversion of ornithine to putrescine in polyamine synthesis, with a subsequent increase in putrescine levels. Inhibition of ornithine decarboxylase via a specific inhibitor, \u03b1-difluoromethylornithine, reduced levels of IL-22 produced by steady-state or IL-23\u2013activated ILC3s in a putrescine-dependent manner. Thus, the polyamine putrescine is a positive regulator of ILC3 activation. Our results suggest that polyamines represent a potential target for therapeutic modulation of ILC3 activation during infection or inflammatory disorders.<\/jats:p>","DOI":"10.4049\/immunohorizons.2200097","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T15:57:43Z","timestamp":1673625463000},"page":"41-48","source":"Crossref","is-referenced-by-count":7,"title":["The Polyamine Putrescine Is a Positive Regulator of Group 3 Innate Lymphocyte Activation"],"prefix":"10.1093","volume":"7","author":[{"given":"Prakash","family":"Sah","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-5955","authenticated-orcid":false,"given":"Lauren A","family":"Zenewicz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"2025010703544603000_r1","doi-asserted-by":"crossref","first-page":"aaa6566","DOI":"10.1126\/science.aaa6566","article-title":"Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology","volume":"348","author":"Eberl","year":"2015","journal-title":"Science"},{"key":"2025010703544603000_r2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41577-019-0194-8","article-title":"Functional interactions between innate lymphoid cells and adaptive immunity","volume":"19","author":"Sonnenberg","year":"2019","journal-title":"Nat. Rev. Immunol"},{"key":"2025010703544603000_r3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/ni.3489","article-title":"Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis","volume":"17","author":"Klose","year":"2016","journal-title":"Nat. Immunol"},{"key":"2025010703544603000_r4","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4049\/immunohorizons.1800006","article-title":"IL-22: there is a gap in our knowledge","volume":"2","author":"Zenewicz","year":"2018","journal-title":"Immunohorizons"},{"key":"2025010703544603000_r5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2021.12.012","article-title":"Metabolic adaptation of lymphocytes in immunity and disease","volume":"55","author":"Chapman","year":"2022","journal-title":"Immunity"},{"key":"2025010703544603000_r6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"O\u2019Neill","year":"2016","journal-title":"Nat. Rev. Immunol"},{"key":"2025010703544603000_r7","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1084\/jem.20180549","article-title":"ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands","volume":"216","author":"Di Luccia","year":"2019","journal-title":"J. Exp. Med"},{"key":"2025010703544603000_r8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cmet.2017.06.019","article-title":"Ancillary activity: beyond core metabolism in immune cells","volume":"26","author":"Puleston","year":"2017","journal-title":"Cell Metab"},{"key":"2025010703544603000_r9","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.it.2020.09.007","article-title":"Polyamines and kynurenines at the intersection of immune modulation","volume":"41","author":"Proietti","year":"2020","journal-title":"Trends Immunol"},{"key":"2025010703544603000_r10","doi-asserted-by":"crossref","first-page":"eabc4275","DOI":"10.1126\/sciadv.abc4275","article-title":"De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function","volume":"6","author":"Wu","year":"2020","journal-title":"Sci. Adv"},{"key":"2025010703544603000_r11","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1073\/pnas.1614958114","article-title":"Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications","volume":"114","author":"Hardbower","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025010703544603000_r12","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cmet.2019.05.003","article-title":"Polyamines and eIF5A hypusination modulate mitochondrial respiration and macrophage activation","volume":"30","author":"Puleston","year":"2019","journal-title":"Cell Metab"},{"key":"2025010703544603000_r13","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1016\/j.cell.2021.06.007","article-title":"Polyamine metabolism is a central determinant of helper T cell lineage fidelity","volume":"184","author":"Puleston","year":"2021","journal-title":"Cell"},{"key":"2025010703544603000_r14","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1016\/j.cell.2021.05.045","article-title":"Metabolic modeling of single Th17 cells reveals regulators of autoimmunity","volume":"184","author":"Wagner","year":"2021","journal-title":"Cell"},{"key":"2025010703544603000_r15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/eji.202048784","article-title":"De novo polyamine synthesis supports metabolic and functional responses in activated murine NK cells","volume":"51","author":"O\u2019Brien","year":"2021","journal-title":"Eur. J. Immunol"},{"key":"2025010703544603000_r16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/mi.2014.71","article-title":"An in vitro model of innate lymphoid cell function and differentiation","volume":"8","author":"Allan","year":"2015","journal-title":"Mucosal Immunol"},{"key":"2025010703544603000_r17","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/ni.3094","article-title":"Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets","volume":"16","author":"Robinette","year":"2015","journal-title":"Nat. Immunol"},{"key":"2025010703544603000_r18","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.cell.2016.07.043","article-title":"The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome","volume":"166","author":"Gury-BenAri","year":"2016","journal-title":"Cell"},{"key":"2025010703544603000_r19","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1172\/JCI70712","article-title":"Inhibition of the aryl hydrocarbon receptor\/polyamine biosynthesis axis suppresses multiple myeloma","volume":"128","author":"Bianchi-Smiraglia","year":"2018","journal-title":"J. Clin. Invest"},{"key":"2025010703544603000_r20","doi-asserted-by":"crossref","first-page":"2579S","DOI":"10.3945\/jn.115.226621","article-title":"Arginine metabolism revisited","volume":"146","author":"Morris","year":"2016","journal-title":"J. Nutr"},{"key":"2025010703544603000_r21","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41568-018-0050-3","article-title":"Polyamine metabolism and cancer: treatments, challenges and opportunities","volume":"18","author":"Casero","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"2025010703544603000_r22","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1038\/jid.2014.146","article-title":"Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients","volume":"134","author":"Teunissen","year":"2014","journal-title":"J. Invest. Dermatol"},{"key":"2025010703544603000_r23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/mi.2013.33","article-title":"IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism","volume":"7","author":"Eken","year":"2014","journal-title":"Mucosal Immunol"},{"key":"2025010703544603000_r24","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20140678","article-title":"CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22","volume":"211","author":"Longman","year":"2014","journal-title":"J. Exp. Med"},{"key":"2025010703544603000_r25","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1172\/JCI61862","article-title":"Ror\u03b3t+ innate lymphocytes and \u03b3\u03b4 T cells initiate psoriasiform plaque formation in mice","volume":"122","author":"Pantelyushin","year":"2012","journal-title":"J. Clin. Invest"},{"key":"2025010703544603000_r26","doi-asserted-by":"crossref","first-page":"18693","DOI":"10.1074\/jbc.TM118.005670","article-title":"Polyamine function in archaea and bacteria","volume":"293","author":"Michael","year":"2018","journal-title":"J. Biol. Chem"},{"key":"2025010703544603000_r27","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1053\/j.gastro.2021.11.005","article-title":"Protective role of spermidine in colitis and colon carcinogenesis. [Published erratum appears in 2022 Gastroenterology 162: 2138\u20132143.]","volume":"162","author":"Gobert","year":"2022","journal-title":"Gastroenterology"},{"key":"2025010703544603000_r28","doi-asserted-by":"crossref","first-page":"e2214900119","DOI":"10.1073\/pnas.2214900119","article-title":"Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription","volume":"119","author":"Peng","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["ImmunoHorizons"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/7\/1\/41\/61339414\/ih2200097.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/7\/1\/41\/61339414\/ih2200097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T04:02:39Z","timestamp":1736222559000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article\/7\/1\/41\/7831876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/immunohorizons.2200097","relation":{},"ISSN":["2573-7732"],"issn-type":[{"value":"2573-7732","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1]]},"published":{"date-parts":[[2023,1,1]]}}}